(1) The localization of human growth hormone releasing factor (GRF) immunoreactive neurons was studied in the rat brain. A dense accumulation of GRF-containing fibers was noted in the external layer of the median eminence. Cell bodies were observed in colchicine-treated rats. The most intensely fluorescent cluster of cells was contained in the arcuate nucleus. Other cells were seen on the base of the hypothalamus, within the median forebrain bundle, dorsal and ventral aspects of the ventromedial nucleus, zona incerta and dorsal part of the dorsomedial nucleus. These cells may influence the pulsatile release of pituitary growth hormone. (2) Corticotropin releasing factor (CRF)-like immunoreactive neurons have been identified in the rat retina by immunohistochemical methods using antisera directed against ovine and rat CRF. CRF-like immunoreactivity was observed in both amacrine and ganglion cells which projected fine varicose processes to the inner plexiform layer of the retina. (3) Treatment of newborn rats with capsaicin (CAP) was shown to cause a disappearance of CRF-like immunoreactive nerve fibers in the dorsal horn of the spinal cord (laminae I and II), the spinal trigeminal nucleus and tract and the nucleus tractus solitarius, but not in the median eminence and the central amygdaloid nucleus. Since it is well known that CAP acts selectively on primary sensory neurons of the C-fiber type, it is suggested that CRF is also located in peripheral sensory neurons, representing a novel peptidergic neuronal system, possibly involved in the modulation of transmission of peripheral nociceptive impulses, which is different from the CAP resistant hypothalamo-infundibular CRF system.